• Media type: E-Article
  • Title: Evaluation of tyrosine kinase receptors in brain metastases of clear cell renal cell carcinoma reveals cMet as a negative prognostic factor
  • Contributor: Schiefer, Ana‐Iris; Mesteri, Ildiko; Berghoff, Anna S; Haitel, Andrea; Schmidinger, Manuela; Preusser, Matthias; Birner, Peter
  • Published: Wiley, 2015
  • Published in: Histopathology
  • Extent: 799-805
  • Language: English
  • DOI: 10.1111/his.12709
  • ISSN: 0309-0167; 1365-2559
  • Keywords: General Medicine ; Histology ; Pathology and Forensic Medicine
  • Abstract: <jats:sec><jats:title>Aims</jats:title><jats:p>Brain metastases (<jats:styled-content style="fixed-case">BM</jats:styled-content>s) of clear cell renal cell carcinoma (cc<jats:styled-content style="fixed-case">RCC</jats:styled-content>) are associated with a dismal prognosis, with limited treatment options. Tyrosine kinases are relevant ‘druggable’ biomarkers. The aim of this study was to evaluate the tyrosine kinase receptors anaplastic lymphoma kinase (<jats:styled-content style="fixed-case">ALK</jats:styled-content>), epidermal growth factor receptor (<jats:styled-content style="fixed-case">EGFR</jats:styled-content>), platelet‐derived growth factor receptor‐α (<jats:styled-content style="fixed-case">PDGFRA</jats:styled-content>) and <jats:styled-content style="fixed-case">cM</jats:styled-content>et in a large series of cc<jats:styled-content style="fixed-case">RCC BM</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p><jats:styled-content style="fixed-case">ALK</jats:styled-content>,<jats:styled-content style="fixed-case"> EGFR</jats:styled-content>,<jats:styled-content style="fixed-case"> PDGFRA</jats:styled-content> and <jats:styled-content style="fixed-case">cM</jats:styled-content>et protein expression was determined by immunohistochemistry in 53 cc<jats:styled-content style="fixed-case">RCC</jats:styled-content>s <jats:styled-content style="fixed-case">BM</jats:styled-content>s and 12 matched primary tumours. <jats:styled-content style="fixed-case">ALK</jats:styled-content> and <jats:styled-content style="fixed-case">MET</jats:styled-content> gene status and copy number alterations of chromosome 7 were studied with fluorescence <jats:italic>in‐situ</jats:italic> hybridization (<jats:styled-content style="fixed-case">FISH</jats:styled-content>). Data on the expression of hypoxia‐inducible factor 1α (<jats:styled-content style="fixed-case">HIF</jats:styled-content>1α) and Ki67 and microvessel density were available from previous studies. <jats:styled-content style="fixed-case">ALK</jats:styled-content> was negative in all analysed specimens. <jats:styled-content style="fixed-case">EGFR</jats:styled-content> was overexpressed in 41 of 51 (80.4%) <jats:styled-content style="fixed-case">BM</jats:styled-content>s and in seven of eight primary tumours, <jats:styled-content style="fixed-case">PDGFRA</jats:styled-content> was overexpressed in all <jats:styled-content style="fixed-case">BM</jats:styled-content>s except one and in all primary tumours, and <jats:styled-content style="fixed-case">cM</jats:styled-content>et was expressed in 26 of 50 (52%) <jats:styled-content style="fixed-case">BM</jats:styled-content>s and in two of seven primary tumours, and did not correlate with <jats:styled-content style="fixed-case">MET</jats:styled-content> amplification or polysomy 7. <jats:styled-content style="fixed-case">cM</jats:styled-content>et was the only parameter associated with significantly shorter <jats:styled-content style="fixed-case">BM</jats:styled-content>‐specific survival (median 8 months versus 33 months, <jats:italic>P</jats:italic> = 0.005, Cox regression).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:styled-content style="fixed-case">EGFR</jats:styled-content>,<jats:styled-content style="fixed-case"> PDGFRA</jats:styled-content> and <jats:styled-content style="fixed-case">cM</jats:styled-content>et are commonly overexpressed in cc<jats:styled-content style="fixed-case">RCC BM</jats:styled-content>s. <jats:styled-content style="fixed-case">cM</jats:styled-content>et overexpression correlates with significantly shorter <jats:styled-content style="fixed-case">BM</jats:styled-content>‐specific survival.</jats:p></jats:sec>
  • Description: <jats:sec><jats:title>Aims</jats:title><jats:p>Brain metastases (<jats:styled-content style="fixed-case">BM</jats:styled-content>s) of clear cell renal cell carcinoma (cc<jats:styled-content style="fixed-case">RCC</jats:styled-content>) are associated with a dismal prognosis, with limited treatment options. Tyrosine kinases are relevant ‘druggable’ biomarkers. The aim of this study was to evaluate the tyrosine kinase receptors anaplastic lymphoma kinase (<jats:styled-content style="fixed-case">ALK</jats:styled-content>), epidermal growth factor receptor (<jats:styled-content style="fixed-case">EGFR</jats:styled-content>), platelet‐derived growth factor receptor‐α (<jats:styled-content style="fixed-case">PDGFRA</jats:styled-content>) and <jats:styled-content style="fixed-case">cM</jats:styled-content>et in a large series of cc<jats:styled-content style="fixed-case">RCC BM</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p><jats:styled-content style="fixed-case">ALK</jats:styled-content>,<jats:styled-content style="fixed-case"> EGFR</jats:styled-content>,<jats:styled-content style="fixed-case"> PDGFRA</jats:styled-content> and <jats:styled-content style="fixed-case">cM</jats:styled-content>et protein expression was determined by immunohistochemistry in 53 cc<jats:styled-content style="fixed-case">RCC</jats:styled-content>s <jats:styled-content style="fixed-case">BM</jats:styled-content>s and 12 matched primary tumours. <jats:styled-content style="fixed-case">ALK</jats:styled-content> and <jats:styled-content style="fixed-case">MET</jats:styled-content> gene status and copy number alterations of chromosome 7 were studied with fluorescence <jats:italic>in‐situ</jats:italic> hybridization (<jats:styled-content style="fixed-case">FISH</jats:styled-content>). Data on the expression of hypoxia‐inducible factor 1α (<jats:styled-content style="fixed-case">HIF</jats:styled-content>1α) and Ki67 and microvessel density were available from previous studies. <jats:styled-content style="fixed-case">ALK</jats:styled-content> was negative in all analysed specimens. <jats:styled-content style="fixed-case">EGFR</jats:styled-content> was overexpressed in 41 of 51 (80.4%) <jats:styled-content style="fixed-case">BM</jats:styled-content>s and in seven of eight primary tumours, <jats:styled-content style="fixed-case">PDGFRA</jats:styled-content> was overexpressed in all <jats:styled-content style="fixed-case">BM</jats:styled-content>s except one and in all primary tumours, and <jats:styled-content style="fixed-case">cM</jats:styled-content>et was expressed in 26 of 50 (52%) <jats:styled-content style="fixed-case">BM</jats:styled-content>s and in two of seven primary tumours, and did not correlate with <jats:styled-content style="fixed-case">MET</jats:styled-content> amplification or polysomy 7. <jats:styled-content style="fixed-case">cM</jats:styled-content>et was the only parameter associated with significantly shorter <jats:styled-content style="fixed-case">BM</jats:styled-content>‐specific survival (median 8 months versus 33 months, <jats:italic>P</jats:italic> = 0.005, Cox regression).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:styled-content style="fixed-case">EGFR</jats:styled-content>,<jats:styled-content style="fixed-case"> PDGFRA</jats:styled-content> and <jats:styled-content style="fixed-case">cM</jats:styled-content>et are commonly overexpressed in cc<jats:styled-content style="fixed-case">RCC BM</jats:styled-content>s. <jats:styled-content style="fixed-case">cM</jats:styled-content>et overexpression correlates with significantly shorter <jats:styled-content style="fixed-case">BM</jats:styled-content>‐specific survival.</jats:p></jats:sec>
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